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Biomedical subjects

A Oehling

Publications and source records attributed to A Oehling.

At least 73 records · Page 4Linked to original sources

Furosemide inhibits in vitro histamine release induced by antigens and anti-IgE.

We used 56 samples of heparinized blood of patients with asthma and/or allergic rhinitis, which were stimulated with Dermatophagoides pteronyssinus or gramineous pollen and anti-IgE in order to study the effect of furosemide on histamine release in basophils. At the same time, blood samples incubated in furosemide in different concentrations (2.5 microM to 1.49 mM) were also subjected to the same stimuli. Results showed a linear and dose-dependent inhibition of histamine release for antigens (r = 0.96; p < 0.01) and anti-IgE (r = 0.95; p < 0.05), reaching 95% at maximum inhibition. These results support the hypothesis that furosemide may act on mastocytes and basophils, thus inhibiting the release of histamine and other mediators.

Allergens↗

[Study of drug allergies with special reference to skin manifestations].

One hundred and forty four patients, with dermal reactions to different drugs, were chosen from our clinic. The selection criteria was based on a detailed and careful anamnesis in order to be certain of the specific drug responsible for the reaction. We tried to establish a drug-specific reaction pattern for each of the drugs studied. Intradermal skin tests were performed with all drugs to be studied, except with pyrazolones and aspirin, for which patch tests were applied. The drug concentrations were established prior to the tests in order to avoid unwanted unspecific reactions. In every case, immediate and delayed reaction readings were carried out. A three crosses reaction (+++) was considered positive. The skin tests were positive in 44% of the cases, a value higher than those referred to by most authors. The delayed reactions to skin tests and the chloramphenicol-mediated delayed-type "dermatitis-like" manifestations are compared. It is noteworthy to mention that positive delayed reactions were observed more frequently with chloramphenicol than with any of the other studied drugs. The same applies for those patients with a positive history to chloramphenicol. The most common reaction pattern to penicillin and streptomycin in our series (20%) were urticaria and Quincke's edema. Penicillin, pyrazolones and streptomycin were the most common drugs responsible for urticarial patterns, being the pyrazolones related to fixed erythema in many cases. The age group 25-50 was the most frequently involved. No sex predominance was observed. The value of the classic skin tests is discussed, so are history recording and the in vitro tests.

Adolescent↗

Variations of intracellular histamine basophil levels after treatment with ketotifen.

As reported in previous studies, ketotifen modifies the number of basophils in peripheral blood, most likely inhibiting their degranulation, which correlates with the lack of exercise-induced respiratory manifestations. In this study, we attempted to measure the approximate amount of intracellular histamine in patients with bronchial asthma sensitized to Dermatophagoides pteronyssinus when they were treated with ketotifen, and compare the values with those of an untreated group and a control group, in order to determine if ketotifen stabilizes the cellular membrane, with the subsequent increase of intracellular mediators. We found that untreated patients had 57% less histamine per basophil than the control group, while treated patients had only 17% less than the controls. This shows that ketotifen acts as a membrane stabilizer, thus inhibiting degranulation and increasing the amount of intracellular mediators.

Adolescent↗

Specific IgG subclasses in pollinosis.

We studied IgG subclasses in pollinosis in order to determine the possible immunopathological role of these antibodies, especially antigen-specific IgG4. The selection of pollinosic patients allowed us to observe the influence natural antigenic exposure exerts upon antibodies. On the other hand, we intended to study the possible modifications immunotherapy produces on IgG subclasses. For this purpose, we selected 266 patients who were classified into the following groups: Group I, 65 patients without immunotherapy, 35 of whom were studied during the pollen season and 30 outside the pollen season; Group II, 40 nonpollinosic patients with hypersensitization to Dermatophagoides pteronyssinus were taken as atopic controls; Group III, 161 pollinosic patients with from 3 to 42 months of immunotherapy. For every patient, IgG1, IgG2 and IgG3 against Phleum pratense were determined by means of ELAST (Leti), and IgG4 against the same allergen by means of the ELISA technique developed by us. Our results confirm, first, that untreated pollinosic patients present higher concentrations of IgG4 against Phleum than nonpollinosic patients, and second, that immunotherapy produces significant modifications in the production of antigen-specific IgG.

Antibody Specificity↗

Effect of ketotifen on phosphodiesterase activity from asthmatic individuals.

It was demonstrated, in this study, that phosphodiesterase activity was elevated in asthmatic patients compared to healthy individuals. This may be reason why various authors found higher intracellular cAMP levels in healthy individuals than in asthmatic patients. We also demonstrated that the efficacy of ketotifen in inhibiting antigen-specific histamine release is due to the potent inhibitor effect of ketotifen on cellular phosphodiesterase activity which then allowed intracellular cAMP accumulation, and as a consequence prevented mediators release.

3',5'-Cyclic-AMP Phosphodiesterases↗

Membrane IgE and adenyl cyclase activity in the dynamics of bronchospasm. Ketotifen as a blocker of antigen action.

A continuous exposition to antigen provokes an increase of IgE synthesis in individuals sensitized to that antigen. This increase in the synthesis is hardly seen to be reflected in seric levels; however, it is clearly seen in the quantity of IgE associated with membranes as this value increases considerably. This fact is due to the characteristic of IgE which tends to fix itself to basophil membrane. On the other hand, although no difference exists in basal adenyl cyclase activity of asthmatic and healthy individuals, the sensitivity of this enzyme to isoproterenol (beta-agonist) is greater in healthy than in asthmatic individuals. The antigenic stimulus makes adenyl cyclase activity descend in these individuals; this does not happen when the cells are treated with ketotifen before stimulating them with the antigen.

Adenylyl Cyclase Inhibitors↗

Does ketotifen act by directly stimulating beta-adrenergic system?

Through this study we proved that the inhibitory effect ketotifen has on antigen-specific histamine release (ASHR) does not have any relation with beta-adrenergic system stimulation. However, it increases the inhibitory effect of histamine release caused by isoproterenol. Therefore, although ketotifen does not directly stimulate beta-adrenergic receptors to inhibit mediator secretion, its action correlates with the response produced through the stimulation of these receptors.

Allergens↗

Effect of ketotifen on the methyltransferase activity of asthmatic patients.

The results of this study have revealed that asthmatic individuals have less methyltransferase activity, compared to healthy individuals. This is reflected in a less fluidity of the plasmatic membrane and thus, presents with less beta-receptors compared to healthy subjects. Ketotifen is capable of partially reversing this situation where it stimulates methyltransferase activity of asthmatic individuals approaching the enzyme activity to healthy individuals.

3',5'-Cyclic-AMP Phosphodiesterases↗

IgE receptors (FcR epsilon) modifications. II. Effect of regulator soluble factors of human IgE synthesis, isolated in polyacrylamide gels.

In a series of works done on humans patterned after animal experimental models, we created an "in vitro" model which allowed us to produce soluble IgE regulator factors. We observed its biological activity in IgE synthesis and constructed changes that protein fractions from affinity chromatography (fractions enriched in soluble regulator IgE factors) exercised on IgE receptor expression. We then decided to determine the molecular weight of each one of the active protein fractions. We performed electrophoresis on the gel of polyacrylamide (Weber-Osborn technique). Protein bands were processed, with the aim of isolating the gel and quantifying the biological activity. The protein fractions obtained from the chromatographies with affinity to CON-A sepharose were subjected to electrophoresis in polyacrylamide gel, with the aim of obtaining molecular weights of proteins comprising it. Using rosette technique, there were no changes seen in Fc epsilon expression just as what happened in the experiment with material fractionated by chromatography. However, these changes are produced and are statistically significant using the immunofluorescence technique. The highest inhibition of rosettes or immunofluorescence is that of the protein band of 10,000 daltons extracted in NaCl and that of 20,000 daltons extracted in PBS. Both effects are similar. The inhibition reached by the 20,000 dalton band in NaCl is less although there are no significant differences. The material extracted in PBS of the band between 6.9 and 7.2 mm of gel (G4) did not have any changes. None of the proteins added to the culture medium had any effects of receptor gamma expression. The average values of the receptor expression was similar to basal levels.

Antigens, Differentiation↗

IgE receptors (FcR epsilon) modifications. I. Effect of regulator soluble factors of human IgE synthesis isolated by affinity chromatography.

After isolating the soluble factors and observing their biological activity of "in vitro" IgE synthesis, we decided to study the changes these molecules exercise on the expression of lymphocytes of IgE (FcR epsilon). We saw that the fractions from healthy subjects inhibited the expression of receptors quantified by immunofluorescence, reducing it to 15.5 and 15.75 (p less than 0.01). Three of the fractions from atopic individuals also inhibited this expression, with some average values of 13.75, 11.25 and 15.25, against 23 as the basal levels. Material from pollinic patients acted similarly, obtaining expression percentages of 13 and 14.5 (p less than 0.01). These findings, along with those obtained in the experiment of IgE synthesis, confirmed the presence of regulator factors in IgE synthesis in the 3 population groups, quantitatively different. These factors will be isotype specific and just as what happened in IgG synthesis, there was no modification in the expression of the mentioned immunoglobulin.

Antigens, Differentiation↗

Decrease of beta-receptors after the antigen-specific bronchial provocation test in bronchial asthma.

Airway hyperreactivity to different stimuli is a characteristic feature of bronchial asthma. The beta-adrenergic theory, as proposed by Szentivanyi in 1968, tried to explain with beta-adrenergic dysfunction, the cause not only of bronchial hyperreactivity but of all atopic diseases. In a previous work, we found that asymptomatic asthmatic patients presented a number of beta-receptors similar to that of a normal control group, while symptomatic asthmatic patients presented a significantly decreased number when compared to both groups (40% decrease). In view of these results, we proposed to study the possible changes in the number of beta-receptors in asymptomatic asthmatic patients after a bronchial provocation test. Fifteen patients, diagnosed of bronchial asthma and sensitive to the house dust mite, D. pteronyssinus, were studied. All were free of medication and asymptomatic at least 90 days before the study. A test of specific bronchial provocation was performed on 10 patients, determining the number of beta-receptors in basal conditions, after 30 minutes and 24 hours. The other five patients underwent an unspecific provocation test with methacholine, with determination of the beta-receptor number at basal conditions, and 24 hours later. Only a significant decrease (30.4%) was found in the beta-receptor numbers, 24 hours after specific bronchial provocation with p less than 0.025 with the Student test for paired data. With regards the beta-adrenergic theory of atopy, in our opinion our results show that the detected decrease of beta-receptors would be the consequence and not the cause of atopic diseases.

Allergens↗

Changes in the lymphocyte response and in the production of IgE regulatory factors in relation to the course of immunotherapy.

In previous studies we described isotype-specific but antigen non-restricted soluble factors produced by human lymphocytes. In subsequent studies we demonstrated changes in the production of these factors during the course of immunotherapy (IT) by testing them on lymphocytes from normal healthy controls and allergic patients. Through these studies we confirmed that there exists a difference in lymphocytes' responsiveness to soluble factors between both groups. In this report, we investigated the effect of soluble factors on lymphocytes from allergic patients without IT (LyG1) and with IT longer than 2 years (LyG4). Peripheral blood samples were collected from healthy controls and allergic patients at different time periods of IT, and bidirectional mixed cultures were performed with the isolated lymphocytes. Supernatants obtained from chromatography were tested on lymphocytes of allergic patients without IT and with IT greater than 2 years to determine their effect on IgE synthesis. Long periods of IT reduce the production of Suppressor Factors (SF) by allergic patients as well as their responsiveness. Long periods of IT increase the responsiveness of lymphocytes of allergic patients to Enhancing Factors (EF) and decrease EF production. We propose a "receptor hypothesis" to explain these events.

Desensitization, Immunologic↗

Value of IgG4 antibodies against foods in atopic dermatitis.

Various authors have linked IgG4 antibodies to biological activities that are apparently contradictory in different studies. On one hand, it has been confirmed that during immunotherapy with inhalant and Hymenoptera venom antigens, an increase is produced in specific IgG4 levels. On the other hand, it has been suggested that these antibodies can intervene in hypersensitivity reactions, basically when these are directed against food antigens. We studied IgG4 levels against milk and egg fractions in patients with atopic dermatitis (AD) (n = 23), and in healthy individuals (n = 20). Patients with AD had significantly much higher IgG4 levels against egg white (24.16 micrograms/ml), egg yolk (9.96 micrograms/ml) and beta-lactoglobulin (10 micrograms/ml) than those found in healthy individuals (6.75, 3.12, 3.35 micrograms/ml, respectively), with no significant differences for alpha-lactalbumin and casein. Patients with AD without hypersensitivity to egg and milk, at the moment of the study, also had significantly higher levels than those of control individuals, against egg white (27.11 micrograms/ml), egg yolk (12 micrograms/ml) and beta-lactoglobulin (11.72 micrograms/ml). There were no differences in IgG4 levels against alpha-lactalbumin, beta-lactoglobulin and casein, when comparing patients with AD and hypersensitivity to milk, and patients with AD without present hypersensitivity to milk. We concluded that patients with AD presented high IgG4 levels against egg and milk fractions, in relation to the healthy population, and that the fraction of milk with the highest antigenic potency was beta-lactoglobulin.

Adolescent↗

Effect of immunotherapy on the production of IgE regulatory soluble factors. The response of normal lymphocytes.

IgE synthesis is controlled not only by antigen-specific mechanism but also by other factors which selectively affect the IgE isotype. Several groups demonstrated that factors released by lymphocytes were involved in this regulation. Our previous investigations were also directed in this field. Immunotherapy improves clinical symptoms in allergic respiratory diseases and produces cellular and humoral changes that affect IgE production. So we decided to investigate if immunotherapy had any influence in the production of soluble factors. Bidirectional mixed cultures were performed with lymphocytes from healthy controls and allergic patients with different time periods of IT, and the supernatants obtained from chromatography were tested to determine their effect on IgE synthesis of normal lymphocytes. IT time periods exerted influence on the production of enhancing factors. Suppressor factors derived from allergic patients had no effect on IgE synthesis of normal lymphocytes.

B-Lymphocytes↗

Lymphocyte response to IgE regulatory factors in allergic patients during the course of immunotherapy.

In previous studies we demonstrated isotype-specific but antigen non-restricted soluble factors produced by human lymphocytes of allergic patients and normal controls. In a subsequent investigation we isolated these soluble factors from allergic patients classified in various groups according to their immunotherapy (IT) time periods and from controls, and we tested them on lymphocytes of healthy controls. Then, we decided to amplify the study to include the effects on allergic patients' lymphocytes. Bidirectional mixed cultures were grown with lymphocytes from healthy controls and allergic patients with different IT time periods and supernatants obtained from chromatography were tested on lymphocytes of twenty-one allergic patients. None of the enhancing factors showed statistical significant effects on IgE synthesis of allergic lymphocytes. There clearly existed a change in the production of suppressor factors during the course of IT, but the long time period of IT did not increase this production.

B-Lymphocytes↗

The inhibitory effect of ketotifen on in vitro histamine release in allergic patients.

Since the discovery of ketotifen as a protective drug of hypersensitivity reactions against an antigen, there have been numerous works that have demonstrated this action both in food and inhalant allergies. In this work we studied the inhibitory capacity of this substance in vitro on the membrane of the basophils of individuals sensitized with positive histamine release test in whole blood against the allergen in question. This was compared with the effect obtained with other drugs (ASA, betamethasone, clemastine, DSCG, oxatomide). Forty-five patients were studied: 30 pollen allergies and 15 with house dust allergy. The results obtained showed the clear action of ketotifen as an inhibitor of histamine released on stimulated basophils with any of the antigens studied. The rest of the substances tested did not demonstrate any significant changes on the histamine released.

Animals↗

Adverse reactions produced by iodinated contrast media.

Given the wide utilization of iodide contrast media for the visualization of the different apparatus of the human being and in the view of the presence of adverse reactions in 50% of the explored patients, we thought it interesting to write this review. In it we intend to show, in a clear and concise way, the different mechanisms implicated in the type of reactions. We also comment on the various actual and future methods that could be useful at the time of detecting and preventing such reactions.

Adrenal Cortex Hormones↗

Action of ketotifen on histamine release and intracellular cAMP levels in basophil cultures from pollinic subjects.

Basophils from peripheral blood of 22 pollinic patients were isolated and were cultured in the presence of different concentrations of ketotifen. We studied the effect of this drug on the specific histamine release (Technicon autoanalyzer) and the levels of intracellular cAMP during days 1, 6 and 12 of culture period. We observed that ketotifen induced an inhibition of specific histamine release throughout the culture days, but was greater on the 12th day. The cAMP levels likewise increased during the period of culture in the presence of ketotifen.

Adult↗